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Intellectual enrichment and genetic modifiers of cognition and brain volume in Huntington's disease
Papoutsi, Marina Flower, Michael Hensman Moss, Davina J. Holmans, Peter Estevez-Fraga, Carlos Johnson, Eileanoir B. Scahill, Rachael I. Rees, Geraint Langbehn, Douglas Tabrizi, Sarah J.
Papoutsi, Marina
Flower, Michael
Hensman Moss, Davina J.
Holmans, Peter
Estevez-Fraga, Carlos
Johnson, Eileanoir B.
Scahill, Rachael I.
Rees, Geraint
Langbehn, Douglas
Tabrizi, Sarah J.
Author
Papoutsi, Marina
Flower, Michael
Hensman Moss, Davina J.
Holmans, Peter
Estevez-Fraga, Carlos
Johnson, Eileanoir B.
Scahill, Rachael I.
Rees, Geraint
Langbehn, Douglas
Tabrizi, Sarah J.
Kraus, Peter
Hoffman, Rainer
Tobin, Alan
Borowsky, Beth
Keenan, S.
Whitlock, Kathryn B.
Queller, Sarah
Campbell, Colin
Wang, Chiachi
Axelson, Eric
Johnson, Hans
Acharya, Tanka
Cash, Dave M.
Frost, Chris
Jones, Rebecca
Jurgens, Caroline
‘t Hart, Ellen P.
Grond, Jeroen van der
Witjes-Ane, Marie-Noelle N.
Roos, Raymund A. C.
Dumas, Eve M.
van den Bogaard, Simon J. A.
Stopford, Cheryl
Craufurd, David
Callaghan, Jenny
Arran, Natalie
Rosas, Diana D.
Lee, S.
Monaco, W.
O’Regan, Alison
Milchman, Cassie
Frajman, Ellen
Labuschagne, Izelle
Stout, Julie
Campbell, Melissa
Andrews, Sophie C.
Bechtel, Natalie
Reilmann, Ralf
Bohlen, Stefan
Kennard, Chris
Berna, Claire
Hicks, Stephen
Durr, Alexandra
Pourchot, Cristophe
Bardinet, Eric
Nigaud, Kevin
Valabrègue, Romain
Lehericy, Stephane
Marelli, Cecilia
Jauffret, Celine
Justo, Damian
Leavitt, Blair
Decolongon, Joji
Sturrock, Aaron
Coleman, Alison
Dar Santos, Rachelle
Patel, Aakta
Gibbard, Claire
Whitehead, Daisy
Wild, Ed
Owen, Gail
Crawford, Helen
Malone, Ian
Lahiri, Nayana
Fox, Nick C.
Hobbs, Nicola Z.
Ordidge, Roger
Pepple, Tracey
Read, Joy
Say, Miranda J.
Landwehrmeyer, Bernhard
Flower, Michael
Hensman Moss, Davina J.
Holmans, Peter
Estevez-Fraga, Carlos
Johnson, Eileanoir B.
Scahill, Rachael I.
Rees, Geraint
Langbehn, Douglas
Tabrizi, Sarah J.
Kraus, Peter
Hoffman, Rainer
Tobin, Alan
Borowsky, Beth
Keenan, S.
Whitlock, Kathryn B.
Queller, Sarah
Campbell, Colin
Wang, Chiachi
Axelson, Eric
Johnson, Hans
Acharya, Tanka
Cash, Dave M.
Frost, Chris
Jones, Rebecca
Jurgens, Caroline
‘t Hart, Ellen P.
Grond, Jeroen van der
Witjes-Ane, Marie-Noelle N.
Roos, Raymund A. C.
Dumas, Eve M.
van den Bogaard, Simon J. A.
Stopford, Cheryl
Craufurd, David
Callaghan, Jenny
Arran, Natalie
Rosas, Diana D.
Lee, S.
Monaco, W.
O’Regan, Alison
Milchman, Cassie
Frajman, Ellen
Labuschagne, Izelle
Stout, Julie
Campbell, Melissa
Andrews, Sophie C.
Bechtel, Natalie
Reilmann, Ralf
Bohlen, Stefan
Kennard, Chris
Berna, Claire
Hicks, Stephen
Durr, Alexandra
Pourchot, Cristophe
Bardinet, Eric
Nigaud, Kevin
Valabrègue, Romain
Lehericy, Stephane
Marelli, Cecilia
Jauffret, Celine
Justo, Damian
Leavitt, Blair
Decolongon, Joji
Sturrock, Aaron
Coleman, Alison
Dar Santos, Rachelle
Patel, Aakta
Gibbard, Claire
Whitehead, Daisy
Wild, Ed
Owen, Gail
Crawford, Helen
Malone, Ian
Lahiri, Nayana
Fox, Nick C.
Hobbs, Nicola Z.
Ordidge, Roger
Pepple, Tracey
Read, Joy
Say, Miranda J.
Landwehrmeyer, Bernhard
Abstract
An important step towards the development of treatments for cognitive impairment in ageing and neurodegenerative diseases is to identify genetic and environmental modifiers of cognitive function and understand the mechanism by which they exert an effect. In Huntington’s disease, the most common autosomal dominant dementia, a small number of studies have identified intellectual enrichment, i.e. a cognitively stimulating lifestyle and genetic polymorphisms as potential modifiers of cognitive function. The aim of our study was to further investigate the relationship and interaction between genetic factors and intellectual enrichment on cognitive function and brain atrophy in Huntington’s disease. For this purpose, we analysed data from Track-HD, a multi-centre longitudinal study in Huntington’s disease gene carriers and focused on the role of intellectual enrichment (estimated at baseline) and the genes FAN1, MSH3, BDNF, COMT and MAPT in predicting cognitive decline and brain atrophy. We found that carrying the 3a allele in the MSH3 gene had a positive effect on global cognitive function and brain atrophy in multiple cortical regions, such that 3a allele carriers had a slower rate of cognitive decline and atrophy compared with non-carriers, in agreement with its role in somatic instability. No other genetic predictor had a significant effect on cognitive function and the effect of MSH3 was independent of intellectual enrichment. Intellectual enrichment also had a positive effect on cognitive function; participants with higher intellectual enrichment, i.e. those who were better educated, had higher verbal intelligence and performed an occupation that was intellectually engaging, had better cognitive function overall, in agreement with previous studies in Huntington’s disease and other dementias. We also found that intellectual enrichment interacted with the BDNF gene, such that the positive effect of intellectual enrichment was greater in Met66 allele carriers than non-carriers. A similar relationship was also identified for changes in whole brain and caudate volume; the positive effect of intellectual enrichment was greater for Met66 allele carriers, rather than for non-carriers. In summary, our study provides additional evidence for the beneficial role of intellectual enrichment and carrying the 3a allele in MSH3 in cognitive function in Huntington’s disease and their effect on brain structure.
Keywords
Huntington’s disease, brain-derived neurotrophic factor, intellectual enrichment, MSH3, cognitive modifiers
Date
2022
Type
Journal article
Journal
Brain Communications
Book
Volume
4
Issue
6
Page Range
1-13
Article Number
Article fcac279
ACU Department
School of Behavioural and Health Sciences
Faculty of Health Sciences
Faculty of Health Sciences
Relation URI
Source URL
Event URL
Open Access Status
Published as ‘gold’ (paid) open access
License
File Access
Open
Open
Open